Resveratrol Bioavailability Analysis
Ian Goddard
http://www.sirtuins.com/life-extension.html
FACT: Almost zero free resveratrol is found in the bloodstream after
oral dosing due to the conjugation of resveratrol with sulfur and
glucuronic acid in the liver. [1,2]
HYPOTHESIS: The evidenced effects of non-oral resveratrol dosing (for
example, in vitro or in vivo by injection) are not available by oral
resveratrol dosing.
Hypothesis Test:
Non-oral Resveratrol Effects
* Blood thinning [3]
* Ischemia protection [4]
* Life extension [5]
Oral Resveratrol Effects
* Blood thinning [6]
* Ischemia protection [7]
* Life extension [8]
ERGO: The hypothesis is falsified since there exists at least three
evidenced effects of non-oral resveratrol that appear to be available
by oral resveratrol. We are thus compelled to adopt the contrary
hypothesis: at least some (if not all) evidenced effects of non-oral
resveratrol are available by oral resveratrol. There are means by
which resveratrol may deliver effect despite hepatic conjugation, but
mechanisms are beyond the scope of this logico-empirical-results
analysis.
(This analysis is expressed in formal logic following its empirical
referents.)
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[1] http://www.hubmed.org/display.cgi?uids=15779070
[2] http://www.hubmed.org/display.cgi?uids=12554065
Non-oral Resveratrol Effects:
[3] British Journal of Pharmacology (1999): "trans-Resveratrol
inhibits human platelet aggregation both in vitro and in vivo."
http://www.nature.com/bjp/journal/v128/n1/full/0702749a.html
[4] Brain Research (2003): "Resveratrol was injected i.p. (30 mg/kg
body weight) [...] This study demonstrated for the first time that
resveratrol, a polyphenolic antioxidant, can cross the blood-brain
barrier and exert protective effects against cerebral ischemic
injury."
http://www.hubmed.org/display.cgi?uids=12470882
[5] Nature (2003): "In yeast, resveratrol mimics calorie restriction
by stimulating Sir2, increasing DNA stability and extending lifespan
by 70%." NOTE: This is an instance of non-oral dosing because yeast
are ahepatic.
http://www.nature.com/nature/journal/v425/n6954/abs/nature01960.html
Oral Resveratrol Effects:
[6] Clinica Chimica Acta (1996): "studies were performed on 24 healthy
males aged 26-45 years [...] commercial juice lowered the IC50 for
thrombin (P < 0.001) whereas the resveratrol-enriched juice caused a
dramatic increase (P < 0.001). [...] We conclude that
trans-resveratrol can be absorbed from grape juice in biologically
active quantities and in amounts that are likely to cause reduction in
the risk of atherosclerosis."
http://www.hubmed.org/display.cgi?uids=8814965
[7] Life Sciences (2005): "Male Balb/C mice were treated with
resveratrol for 7 days (50 mg/kg, gavage). [...] elevated levels of
MMP-9 were significantly attenuated in the resveratrol-treated mice as
compared to the vehicle MCAo mice. The study suggests that resveratrol
has protective effects against acute ischemic stroke." NOTE: Feeding
by "gavage" is tube-to-stomach feeding, which does not bypass the
liver.
http://www.hubmed.org/display.cgi?uids=16321402
[8] Current Biology (2006): "120 mg/g [ resveratrol / food ] caused an
increase of median and maximum lifespan of 33% and 27%, respectively
(p < 0.001, log rank test), and 600 mg/g food induced 56% and 59%
increase in median and maximum lifespan, respectively (p < 0.001, log
rank test). 600 mg/g food was significantly more effective than 120
mg/g food in prolonging lifespan (p = 0.01, log rank test)."
http://www.hubmed.org/display.cgi?uids=16461283
Progress of resveratrol life-extension research:
http://www.longevinex.com/images/resveratrol_experiments_full.jpg
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Translating the hypothesis into formal logic for evaluation where
N = non-oral resveratrol dosing
O = oral resveratrol dosing
HYPOTHESIS: The evidenced effects of N are not available by O.
HYPOTHESIS-TEST STATEMENT:
If X is an effect of N, then X is not an effect of O.
Fleshing out that statement for clarity of translation:
For any effect X and any studies x and y, if x uses N and x finds X,
then it is NOT the case that if y uses O, y finds X.
Now translating it into second-order predicate logic:
(X)(x)(y)[ (Nx & Xx) -> ~(Oy -> Xy) ]
(I'll avoid stipulating that x =/= y for brevity)
Now instantiating it step-by-step into the first empirical case where
B = found blood-thinning
a = study [3]
b = study [6]
1. (X)(x)(y)[ (Nx & Xx) -> ~(Oy -> Xy) ]
2. (x)(y)[ (Nx & Bx) -> ~(Oy -> By) ]
3. (y)[ (Na & Ba) -> ~(Oy -> By) ]
4. (Na & Ba) -> ~(Ob -> Bb)
And then applying two replacement rules to step 4:
4. (Na & Ba) -> ~(Ob -> Bb)
5. (Na & Ba) -> ~(~Ob v Bb) - conditional exchange
6. (Na & Ba) -> (Ob & ~Bb) - de Morgan's
Now by the semantics of predicate logic we can see that the
hypothesis-test statement is false by observing that its antecedent
(Na & Ba) is true (study [3] has the properties N and B), yet its
consequent is false because in fact b (study [6]) has the properties O
and B. However, according to the hypothesis-test statement, b must
have the property ~B. So it turns out that ~Bb is false since Bb is
true, and thus the consequent (Ob & ~Bb) is false since one of its
conjuncts is false. Therefore, with a true antecedent and false
consequent, the whole statement (Ba & Na) -> (Ob & ~Bb) is false, and
thus the hypothesis is falsified by this single case alone.
Instantiating the hypothesis-test statement into the other two cases
cited above follows same steps to the same result.
Because the hypothesis is falsified we must by logical consequence
adopt the contrary: at least some (if not all) evidenced effects of
non-oral resveratrol are available by oral resveratrol.
"Without philosophy thoughts are, as it were, cloudy and indistinct;
its task is to make them clear and to give them sharp boundaries."
Ludwig Wittgenstein